Identifying iNOS and glycogen as biomarkers for degenerated cerebellar purkinje cells in autism spectrum disorder: Protective effects of erythropoietin and zinc sulfate
Al-Garni, Abdulaziz M Hosny, Sara A Almasabi, Faris Shati, Ayed A Alzamil, Norah M ShamsEldeen, Asmaa M El-Shafei, Asmaa A Al-Hashem, Fahaid Zafrah, Hind Maarouf, Amro
Al-Garni, Abdulaziz M
Hosny, Sara A
Almasabi, Faris
Shati, Ayed A
Alzamil, Norah M
ShamsEldeen, Asmaa M
El-Shafei, Asmaa A
Al-Hashem, Fahaid
Zafrah, Hind
Maarouf, Amro
Citations
Altmetric:
Affiliation
King Khalid University; Queens University; The Dudley Group NHS Foundation Trust et al
Other Contributors
Publication date
2025-02-13
Subject
Collections
Research Projects
Organizational Units
Journal Issue
Abstract
Autism spectrum disorder (ASD) is a collective neurodevelopmental disorder affecting young children and accounting for 1% of the world's population. The cerebellum is the major part of the human brain affected by ASD and is associated with a substantial reduction in the number of Purkinje cells. An association between ASD and the expression of the nitrosative stress biomarker inducible nitric oxide synthase (iNOS), as well as glycogen deposition in damaged Purkinje cells, has not been previously reported in the medical literature. To explore this correlation, young rats were injected with propionic acid (PPA) (500 mg/kg) for 5 days (model group), while the protection groups were treated with either erythropoietin (EPO, 5,000 U/kg) or 2 mg/kg zinc sulfate immediately after the PPA injections. ASD-like features were developed in the model group, as evidenced by cerebellum damage (degeneration of Purkinje cells) and cerebellar dysfunction (behavioral impairment). This study documented the exclusive expression of iNOS in the degenerated Purkinje cells, along with glycogen deposition in these cells. Additionally, PPA significantly (p < 0.001) modulated cerebellar tissue levels of mammalian target of rapamycin (mTOR), gamma-aminobutyric acid (GABA), GABAA receptor, serotonin, the marker of neuronal loss (calbindin D28K), and social interaction deficit. Some of these parameters were differentially protected by EPO and zinc sulfate, with the former providing greater protection than zinc sulfate. Furthermore, a significant correlation between the iNOS score and these parameters associated with ASD was observed. These findings demonstrate the colocalization of iNOS and glycogen in the damaged Purkinje cells induced by ASD, along with the modulation of ASD parameters, which were protected by EPO and zinc sulfate treatments. Thus, these potential novel biomarkers may offer possible therapeutic targets for the treatment of ASD. Competing Interests: The authors have declared that no competing interests exist. Copyright: 2025 Al-Garni et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation
Al-Garni AM, Hosny SA, Almasabi F, Shati AA, Alzamil NM, ShamsEldeen AM, El-Shafei AA, Al-Hashem F, Zafrah H, Maarouf A, Al-Ani B, Bin-Jaliah I, Kamar SS. Identifying iNOS and glycogen as biomarkers for degenerated cerebellar purkinje cells in autism spectrum disorder: Protective effects of erythropoietin and zinc sulfate. PLoS One. 2025 Feb 13;20(2):e0317695. doi: 10.1371/journal.pone.0317695